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Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Lymphomas

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

rivogenlecleucel

Rimiducid

About this trial

This is an interventional treatment trial for Leukemia focused on measuring BPX-501, Rimiducid, AP1903, Hematological malignancies, Hematologic diseases, Leukemias and Myelodysplastic Syndromes, Lymphomas, Multiple myeloma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects aged ≥ 18 yrs and ≤ 65 yrs;
Clinical diagnosis of one of the following hematological malignancies:
- Leukemia
- Myelodysplastic Syndromes
- Lymphomas
- Multiple Myeloma
- Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard;
Recurrent disease that presents ≥100 days after, or minimal residual disease (MRD) that presents ≥ 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP);
Life expectancy >10 weeks;
Signed donor and patient/guardian informed consent;
A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1;
Performance status: Karnofsky score > 50%;
Subjects with adequate organ function as measured by:
- Bone marrow:
  - > 25% donor T-cell chimerism post-transplant
  - Absolute neutrophil count (ANC) >1 x 109/L
- Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 45%
- Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) ≥ 50% predicted (corrected for hemoglobin)
- Hepatic: direct bilirubin ≤ 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5x ULN
- Renal: creatinine ≤ 2x of ULN for age.

Exclusion Criteria:

≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening;
Active central nervous system (CNS) involvement with malignant cells (≤ 2 months prior to consenting);
Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion;
Positive HIV serology or viral RNA;
Pregnancy (positive serum β human chorionic gonadotropin [HCG] test) or breast-feeding;
Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation;
Bovine product allergy.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rivogenlecleucel & Rimiducid

Arm Description

All subjects will receive 3 courses of rivogenlecleucel (BPX-501 T cells) infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0 and DL2 on Days 30 and 60. Escalating doses of rimiducid (AP1903) (0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after rivogenlecleucel infusion.

Outcomes

Primary Outcome Measures

Adverse events

Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety

Secondary Outcome Measures

Full Information

NCT ID

NCT02786485

First Posted

May 26, 2016

Last Updated

October 1, 2020

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02786485

Brief Title

Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

Official Title

A Phase I Study of Matched Unrelated Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Withdrawn

Study Start Date

May 2016 (Actual)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bellicum Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a Phase I, multicenter, open-label, non-randomized study of matched unrelated donor BPX-501 T cell infusion in adult subjects with hematological malignancies presenting with recurrent disease minimal residual disease (MRD) post-allogeneic transplant.

Detailed Description

Un-manipulated donor lymphocyte infusion (DLI) is used after stem cell transplantation to treat and prevent relapse, to prevent infections and to establish full donor chimerism. The addition of mature T cells which exhibit a broad repertoire of T cell immunity against viral antigens, as well as against cancer antigens, might provide a clinical benefit. However, an expected side effect of the presence of mature T cells is the potential occurrence of acute graft-versus-host disease (aGvHD). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve higher clinical response rate with lower GvHD occurrence. Optimization of DLI dose and schedule as well as strategies of donor T-cell manipulation may lead to the consistent ability to separate GvHD from graft-versus-tumor (GvT) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults and children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myelodysplastic Syndromes, Lymphomas, Multiple Myeloma, Other High-risk Hematological Malignancies

Keywords

BPX-501, Rimiducid, AP1903, Hematological malignancies, Hematologic diseases, Leukemias and Myelodysplastic Syndromes, Lymphomas, Multiple myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rivogenlecleucel & Rimiducid

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

rivogenlecleucel

Other Intervention Name(s)

BPX-501

Intervention Description

T cells transduced with iCasp safety switch

Intervention Type

Drug

Intervention Name(s)

Rimiducid

Other Intervention Name(s)

AP1903

Intervention Description

administered to treat GVHD

Primary Outcome Measure Information:

Title

Adverse events

Description

Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety

Time Frame

30 days after last dose of study drug (BPX-501 and/or rimiducid)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects aged ≥ 18 yrs and ≤ 65 yrs; Clinical diagnosis of one of the following hematological malignancies: Leukemia Myelodysplastic Syndromes Lymphomas Multiple Myeloma Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard; Recurrent disease that presents ≥100 days after, or minimal residual disease (MRD) that presents ≥ 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP); Life expectancy >10 weeks; Signed donor and patient/guardian informed consent; A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1; Performance status: Karnofsky score > 50%; Subjects with adequate organ function as measured by: Bone marrow: > 25% donor T-cell chimerism post-transplant Absolute neutrophil count (ANC) >1 x 109/L Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 45% Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) ≥ 50% predicted (corrected for hemoglobin) Hepatic: direct bilirubin ≤ 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5x ULN Renal: creatinine ≤ 2x of ULN for age. Exclusion Criteria: ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening; Active central nervous system (CNS) involvement with malignant cells (≤ 2 months prior to consenting); Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion; Positive HIV serology or viral RNA; Pregnancy (positive serum β human chorionic gonadotropin [HCG] test) or breast-feeding; Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation; Bovine product allergy.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bellicum Pharmaceuticals

Organizational Affiliation

Bellicum Pharmaceuticals, Inc.

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

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